Muscarinic receptors in the mammalian heart.

In the mammalian heart, cardiac function is under the control of the sympathetic and parasympathetic nervous system. All regions of the mammalian heart are innervated by parasympathetic (vagal) nerves, although the supraventricular tissues are more densely innervated than the ventricles. Vagal activation causes stimulation of cardiac muscarinic acetylcholine receptors (M-ChR) that modulate pacemaker activity via I(f) and I(K.ACh), atrioventricular conduction, and directly (in atrium) or indirectly (in ventricles) force of contraction. However, the functional response elicited by M-ChR-activation depends on species, age, anatomic structure investigated, and M-ChR-agonist concentration used. Among the five M-ChR-subtypes M(2)-ChR is the predominant isoform present in the mammalian heart, while in the coronary circulation M(3)-ChR have been identified. In addition, evidence for a possible existence of an additional, not M(2)-ChR in the heart has been presented. M-ChR are subject to regulation by G-protein-coupled-receptor kinase. Alterations of cardiac M(2)-ChR in age and various kinds of disease are discussed.